Download Adaptive versus innate immune mechanisms in trout responding to

Adptive versus innate immune mechanisms in trout responding to rhabdovirus antigens.
Niels Lorenzen, Senior Research Scientist,
National Veterinary Institute, Technical University of Denmark
Early studies with attenuated vaccine preparations demonstrated that it is possible to induce
protective immunity to virulent rhabdoviruses such as viral haemorrhagic septicaemia virus
(VHSV) and infectious haematopoietic necrosis virus (IHNV) in trout. Little was known about the
nature of the protective mechanisms. Cross-protection following inoculation of fish with less
pathogenic virus forms suggested that innate nonspecific antiviral activities could be involved.
Other data pointed towards adaptive mechanisms. Survivors of infection were immune for several
weeks and complement dependent virus neutralizing antibodies could be detected in serum, and
although the reactivity of such sera in immunoblotting was inconsistent, some reactivity particularly
with the viral surface glycoprotein (G-protein) could be detected. Passive immunization
experiments using neutralizing monoclonal antibodies accordingly demonstrated that antibodies
against the G-protein were protective and pointed towards this protein as a potential vaccine
candidate. However, vaccination using recombinant G protein induced only limited protection and it
was not until DNA vaccination technology was introduced that the capacity of the viral G protein to
induce protective immunity was clearly demonstrated. Cross protection experiments revealed a twophase scenario concerning protective mechanisms with an early antiviral phase with interferon
related innate protection followed by a later and more long lasting period of specific immunity.
Temperature is known to affect immune mechanisms in fish and to delay development of adaptive
immunity, but interestingly, DNA vaccination protects very well throughout a wide temperature
range. Innate protective mechanisms were found to be of much longer duration at 5C compared to
15C, hereby compensating for delayed specific protection. These findings suggest that fish may
depend more on innate immune mechanisms as defence against infections at low temperatures. Still,
at higher temperatures, innate antiviral mechanisms are also very important as the first line defence
against infection of naïve fish. However, a rapid interference with propagation of an infection by
innate mechanisms might prevent development of adaptive immunity. Persistence of antigen in
sufficient amounts to trigger adaptive mechanisms is therefore a critical parameter in terms of
vaccination. DNA vaccination trials with very small rainbow trout fry also induced high level of
protection, but the level of specificity, i.e. involvement of innate vs adaptive immune mechanisms,
remains to be determined.